1. Field of the invention
The invention relates to methods and substances comprising a biocompatible, non-degradable polymer of stable volume for the purpose of augmenting mammalian tissue.
2. Background
This invention relates to synthetic surgical tissue adhesives, tissue sealants and tissue bulking agents, created by reacting an adhesive tissue reactive injectable with living in situ tissue. More specifically, a tissue cross-linked polyurea-urethane bond is formed by reaction of isocyanate capped alkylene oxide diols, triols or polyols with living tissue forms an immobilized, non-biodegradable augmentation of tissue.
Numerous bulking and plastic surgery applications and patents have been published, but none of them teach bulking by means of the novel substance disclosed here and further none of them provide adhesion to tissue. Thus, in the prior art, there is susceptibility to implant migration because of lack of adhesion. Moreover, the present invention is biocompatible. Prior art bulking substances are also known to be biocompatible, but they are also biodegradable. Biodegradability of an implant in a tissue augmentation procedure is generally not desirable since the benefits conferred by the implanted substance disappear with time.
U.S. Pat. No. 5,785,642 (Wallace et al.) describes a 3-part injectable polymer for treating incontinence. While the patent claims improved resistance to migration, principally when compared with particulate injectables, it does not describe a tissue bond to guard against implant migration. Furthermore, the disclosed invention involves forming a polymer precipitate in situ from a solvent/polymer system. Since the solvent does not entirely become part of the precipitate, then some of the injected solvent volume is eventually lost to absorption into the surrounding tissue. Thus, the invention does not teach a device which has a stable volume once implanted.
U.S. Pat. No. 5,712,252 (Smith) describes a method of augmenting soft tissue in a mammal, which includes injecting keratin into soft tissue. Keratin is a biodegradable substance.
U.S. Pat. No. 5,763,399 (Lee) describes a composition and method for effective revitalization of scar tissue by injecting a bioactive substance having angiogenic activity. The revitalization of scar tissue is intended to augment existing tissue. However, this invention cannot control the extent of augmentation.
U.S. Pat. No. 5,922,025 (Hubbard) describes a permanent, biocompatible material for soft tissue augmentation. The biocompatible material comprises a matrix of smooth, round, finely divided, substantially spherical particles of a biocompatible ceramic material. However, prevention of migration of the ceramic material is not described.
U.S. Pat. No. 5,976,526 (Atala) describes treatment of vesicoureteral reflux, incontinence and other defects using an injectable of bladder cells mixed with a liquid polymeric material. This material is susceptible to biodegradation.
U.S. Pat. No. 5,855,615 (Bley at al) describes a composition for injecting into the urethra comprising a plurality of physiologically acceptable solid polymer particles dispersed in a physiologically acceptable biodissipatable liquid carrier. The solid polymer particles are capable of hydrating to a predetermined volume. The injection volume is therefore not necessarily the same as the final hydrated volume.
U.S. Pat. No. 5,709,854 (Griffith-Cima et al) describes a cell polymeric solution that self-cross-links, but does not bond to tissue, for the purpose of inducing tissue formation.
One of the primary uses of the present invention is treatment of urinary incontinence. In particular, many women suffer from incontinence caused by childbirth or obesity. The initial treatment for stress incontinence is exercise to strengthen the pelvic floor muscles. If these exercises are ineffective, open surgical repair of the bladder neck is often attempted. Such surgical repair procedures are not successful for all patients. There is also risk associated with open surgical procedures, such as trauma, infection, and risks of anesthesia.
As an alternative to surgical repair, urinary incontinence has been treated by injecting various substances into the tissue surrounding the urethra, i.e., the periurethral tissue, to add bulk to this tissue. The aim of this treatment is to compress the urethra at the level of the bladder neck to impede involuntary flow of urine from the bladder.
Murless has reported the use of sodium morrhuate for the treatment of stress incontinence (J. Obstet. Gynaecol., 45:67-71(1938)). This material was not successful in treating incontinence and pulmonary infarction was an observed complication. Paraffin (Acta Urol. Belg., 23:259-262(1955)) and other sclerosing solutions (Urol. Int., 15:225-244(1963)) have been tried yielding poor results.
Polytetrafluoroethylene particles (TEFLON™, POLYTEF™) have been used as injectable bulking material with a success rate from 30% to 86% in some studies (J. Urol., 111:180-183(1974); Br. J. Urol., 55:208-210(1983) 210(1983); BMJ 228; 192 (1984); J. Urol., (Paris), 62:39-41(1987); Br. J. Urol., 62:39-41 (1988); Aust. N. Z. J. Surg., 61:663-666 (1966)). The complications associated with this procedure were foreign body granulomas that tended to migrate to distant organs, such as the lungs, liver, spleen and brain (JAMA, 251:3227-3281 (1984)).
Another injectable used recently is glutaraldehyde cross-linked bovine dermal collagen (Med. J. Aust., 158:89-91 (1993); Br. J. Urol., 75:359-363 (1995); Br. J. Urol., 75: 538-542 (1993)). A major problem with the use of collagen was biodegradation with associated decrease in implant volume over time necessitating retreatment (J. Urol., 150:745-747 (1993)). Collagen can also cause adverse immune responses and allergic reactions to bovine collagen have been described (Br. J. Urol., 75:359-363 (1995)).
Other materials have been suggested for use in the treatment of vesicourectal reflux. These substances include polyvinyl alcohol foam (J Urol., 144:531-533 (1990)), glass particles (J. Urol., 148:645 (1992)), a chondrocyte-alginate suspension (J. Urol., 150:745-747 (1993)) and a detachable silicone balloon (J. Urol., 148:724-728 (1992)), each of these cited journal article being incorporated herein by reference.
Injectables have not been suggested for treatment of gastroesophageal reflux disease (GERD), but such use of the disclosed material of this application is envisioned. The material may be injected into the wall of the esophagus to thicken the wall and narrow the gastroesophageal junction into the stomach.
In addition to the need for an immobilized, volume-constant, biocompatible implant, there is also a need to be able to visualize the volume of injected material during and after implantation. It would be preferred to monitor the implant size by non-invasive means. Furthermore, fluoroscopic imaging of the implant would aid in estimation of the implant size and location if follow-up injections are necessary.
In addition, polymerization time of the injected material is an important parameter since the material is typically delivered as a low viscosity solution that may leak from the site after needle removal. The lower the viscosity of the injectable the smaller the needle that may be used.
Finally, there are several pragmatic considerations. For example, the injectable material should not polymerize in the needle of the delivery device so as to necessitate replacement of the needle during the procedure. The solution should be of low viscosity to enable easy delivery of the solution through a 23 G needle.